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J Exp Med. 2016 Sep 19;213(10):2099-112. doi: 10.1084/jem.20160059. Epub 2016 Aug 22.

Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion.

Author information

1
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
2
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
3
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 mlorena@jhsph.edu.

Abstract

Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine.

PMID:
27551151
PMCID:
PMC5030802
DOI:
10.1084/jem.20160059
[Indexed for MEDLINE]
Free PMC Article

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